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. 1989 Dec 1;8(12):3627–3632. doi: 10.1002/j.1460-2075.1989.tb08536.x

Differential brain expression of the Alzheimer's amyloid precursor protein.

J P Anderson 1, L M Refolo 1, W Wallace 1, P Mehta 1, M Krishnamurthi 1, J Gotlib 1, L Bierer 1, V Haroutunian 1, D Perl 1, N K Robakis 1
PMCID: PMC402044  PMID: 2583112

Abstract

The expression of the Alzheimer amyloid protein precursor (AAPP) was examined in human, monkey, dog and rat brains. Two proteins, one identified as AAPP695 and the other as AAPP751, were immunoprecipitated from the in vitro translation of human, dog and rat brain polysomes. The AAPP751 to AAPP695 ratio was highest in human, intermediate in dog and lowest in rat brain polysomes. Human cerebral cortex contained higher levels of the AAPP751 mRNA than either dog or rat cortex. AAPP695 was detected in both cerebral cortex and cerebellum of all species examined. In contrast, AAPP751 was detected predominantly in the cortex of human, monkey and to a lesser extent dog brains while it was not detected in rat brain. These findings indicate that the amyloid precursors are differentially expressed in different mammalian brains and suggest that AAPP751 is mainly expressed in the brain regions involved in plaque formation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson J., Wallace W., Snyder S., Haroutunian V., Roberts J. L., Lieberburg I. Cellular forms of the rat and human beta-amyloid precursor protein (BAPP). Brain Res. 1989 Jan 30;478(2):391–398. doi: 10.1016/0006-8993(89)91523-0. [DOI] [PubMed] [Google Scholar]
  2. Blessed G., Tomlinson B. E., Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry. 1968 Jul;114(512):797–811. doi: 10.1192/bjp.114.512.797. [DOI] [PubMed] [Google Scholar]
  3. Card J. P., Meade R. P., Davis L. G. Immunocytochemical localization of the precursor protein for beta-amyloid in the rat central nervous system. Neuron. 1988 Nov;1(9):835–846. doi: 10.1016/0896-6273(88)90131-6. [DOI] [PubMed] [Google Scholar]
  4. Cunningham B. A., Hemperly J. J., Murray B. A., Prediger E. A., Brackenbury R., Edelman G. M. Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing. Science. 1987 May 15;236(4803):799–806. doi: 10.1126/science.3576199. [DOI] [PubMed] [Google Scholar]
  5. Dayan A. D. Comparative neuropathology of ageing. Studies on the brains of 47 species of vertebrates. Brain. 1971;94(1):31–42. doi: 10.1093/brain/94.1.31. [DOI] [PubMed] [Google Scholar]
  6. Dyrks T., Weidemann A., Multhaup G., Salbaum J. M., Lemaire H. G., Kang J., Müller-Hill B., Masters C. L., Beyreuther K. Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease. EMBO J. 1988 Apr;7(4):949–957. doi: 10.1002/j.1460-2075.1988.tb02900.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Glenner G. G. Alzheimer's disease: its proteins and genes. Cell. 1988 Feb 12;52(3):307–308. doi: 10.1016/s0092-8674(88)80021-7. [DOI] [PubMed] [Google Scholar]
  8. Glenner G. G., Wong C. W. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984 May 16;120(3):885–890. doi: 10.1016/s0006-291x(84)80190-4. [DOI] [PubMed] [Google Scholar]
  9. Goldgaber D., Lerman M. I., McBride O. W., Saffiotti U., Gajdusek D. C. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science. 1987 Feb 20;235(4791):877–880. doi: 10.1126/science.3810169. [DOI] [PubMed] [Google Scholar]
  10. Johnson S. A., Pasinetti G. M., May P. C., Ponte P. A., Cordell B., Finch C. E. Selective reduction of mRNA for the beta-amyloid precursor protein that lacks a Kunitz-type protease inhibitor motif in cortex from Alzheimer brains. Exp Neurol. 1988 Nov;102(2):264–268. doi: 10.1016/0014-4886(88)90104-5. [DOI] [PubMed] [Google Scholar]
  11. Julien J. P., Mushynski W. E. Multiple phosphorylation sites in mammalian neurofilament polypeptides. J Biol Chem. 1982 Sep 10;257(17):10467–10470. [PubMed] [Google Scholar]
  12. KIDD M. ALZHEIMER'S DISEASE--AN ELECTRON MICROSCOPICAL STUDY. Brain. 1964 Jun;87:307–320. doi: 10.1093/brain/87.2.307. [DOI] [PubMed] [Google Scholar]
  13. Kang J., Lemaire H. G., Unterbeck A., Salbaum J. M., Masters C. L., Grzeschik K. H., Multhaup G., Beyreuther K., Müller-Hill B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature. 1987 Feb 19;325(6106):733–736. doi: 10.1038/325733a0. [DOI] [PubMed] [Google Scholar]
  14. Kang J., Müller-Hill B. The sequence of the two extra exons in rat preA4. Nucleic Acids Res. 1989 Mar 11;17(5):2130–2130. doi: 10.1093/nar/17.5.2130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kirschner D. A., Inouye H., Duffy L. K., Sinclair A., Lind M., Selkoe D. J. Synthetic peptide homologous to beta protein from Alzheimer disease forms amyloid-like fibrils in vitro. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6953–6957. doi: 10.1073/pnas.84.19.6953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kitaguchi N., Takahashi Y., Tokushima Y., Shiojiri S., Ito H. Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature. 1988 Feb 11;331(6156):530–532. doi: 10.1038/331530a0. [DOI] [PubMed] [Google Scholar]
  17. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  18. Langstrom N. S., Anderson J. P., Lindroos H. G., Winblad B., Wallace W. C. Alzheimer's disease-associated reduction of polysomal mRNA translation. Brain Res Mol Brain Res. 1989 Jun;5(4):259–269. doi: 10.1016/0169-328x(89)90060-0. [DOI] [PubMed] [Google Scholar]
  19. Manning R. W., Reid C. M., Lampe R. A., Davis L. G. Identification in rodents and other species of an mRNA homologous to the human beta-amyloid precursor. Brain Res. 1988 Jun;427(3):293–297. doi: 10.1016/0169-328x(88)90052-6. [DOI] [PubMed] [Google Scholar]
  20. Masters C. L., Simms G., Weinman N. A., Multhaup G., McDonald B. L., Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245–4249. doi: 10.1073/pnas.82.12.4245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Neve R. L., Finch E. A., Dawes L. R. Expression of the Alzheimer amyloid precursor gene transcripts in the human brain. Neuron. 1988 Oct;1(8):669–677. doi: 10.1016/0896-6273(88)90166-3. [DOI] [PubMed] [Google Scholar]
  22. Palmert M. R., Podlisny M. B., Witker D. S., Oltersdorf T., Younkin L. H., Selkoe D. J., Younkin S. G. Antisera to an amino-terminal peptide detect the amyloid protein precursor of Alzheimer's disease and recognize senile plaques. Biochem Biophys Res Commun. 1988 Oct 14;156(1):432–437. doi: 10.1016/s0006-291x(88)80859-3. [DOI] [PubMed] [Google Scholar]
  23. Ponte P., Gonzalez-DeWhitt P., Schilling J., Miller J., Hsu D., Greenberg B., Davis K., Wallace W., Lieberburg I., Fuller F. A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature. 1988 Feb 11;331(6156):525–527. doi: 10.1038/331525a0. [DOI] [PubMed] [Google Scholar]
  24. Robakis N. K., Ramakrishna N., Wolfe G., Wisniewski H. M. Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4190–4194. doi: 10.1073/pnas.84.12.4190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Robakis N. K., Wisniewski H. M., Jenkins E. C., Devine-Gage E. A., Houck G. E., Yao X. L., Ramakrishna N., Wolfe G., Silverman W. P., Brown W. T. Chromosome 21q21 sublocalisation of gene encoding beta-amyloid peptide in cerebral vessels and neuritic (senile) plaques of people with Alzheimer disease and Down syndrome. Lancet. 1987 Feb 14;1(8529):384–385. doi: 10.1016/s0140-6736(87)91754-5. [DOI] [PubMed] [Google Scholar]
  26. Schubert D., Schroeder R., LaCorbiere M., Saitoh T., Cole G. Amyloid beta protein precursor is possibly a heparan sulfate proteoglycan core protein. Science. 1988 Jul 8;241(4862):223–226. doi: 10.1126/science.2968652. [DOI] [PubMed] [Google Scholar]
  27. Selkoe D. J., Bell D. S., Podlisny M. B., Price D. L., Cork L. C. Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease. Science. 1987 Feb 20;235(4791):873–877. doi: 10.1126/science.3544219. [DOI] [PubMed] [Google Scholar]
  28. Selkoe D. J., Podlisny M. B., Joachim C. L., Vickers E. A., Lee G., Fritz L. C., Oltersdorf T. Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7341–7345. doi: 10.1073/pnas.85.19.7341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shivers B. D., Hilbich C., Multhaup G., Salbaum M., Beyreuther K., Seeburg P. H. Alzheimer's disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact. EMBO J. 1988 May;7(5):1365–1370. doi: 10.1002/j.1460-2075.1988.tb02952.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tanzi R. E., Gusella J. F., Watkins P. C., Bruns G. A., St George-Hyslop P., Van Keuren M. L., Patterson D., Pagan S., Kurnit D. M., Neve R. L. Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science. 1987 Feb 20;235(4791):880–884. doi: 10.1126/science.2949367. [DOI] [PubMed] [Google Scholar]
  31. Tanzi R. E., McClatchey A. I., Lamperti E. D., Villa-Komaroff L., Gusella J. F., Neve R. L. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature. 1988 Feb 11;331(6156):528–530. doi: 10.1038/331528a0. [DOI] [PubMed] [Google Scholar]
  32. Terry R. D., Peck A., DeTeresa R., Schechter R., Horoupian D. S. Some morphometric aspects of the brain in senile dementia of the Alzheimer type. Ann Neurol. 1981 Aug;10(2):184–192. doi: 10.1002/ana.410100209. [DOI] [PubMed] [Google Scholar]
  33. Tomlinson B. E., Blessed G., Roth M. Observations on the brains of non-demented old people. J Neurol Sci. 1968 Sep-Oct;7(2):331–356. doi: 10.1016/0022-510x(68)90154-8. [DOI] [PubMed] [Google Scholar]
  34. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Vaughan D. W., Peters A. The structure of neuritic plaque in the cerebral cortex of aged rats. J Neuropathol Exp Neurol. 1981 Jul;40(4):472–487. doi: 10.1097/00005072-198107000-00009. [DOI] [PubMed] [Google Scholar]
  36. Weidemann A., König G., Bunke D., Fischer P., Salbaum J. M., Masters C. L., Beyreuther K. Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein. Cell. 1989 Apr 7;57(1):115–126. doi: 10.1016/0092-8674(89)90177-3. [DOI] [PubMed] [Google Scholar]
  37. Wiśniewski H. M., Bruce M. E., Fraser H. Infectious etiology of neuritic (senile) plaques in mice. Science. 1975 Dec 12;190(4219):1108–1110. doi: 10.1126/science.1237933. [DOI] [PubMed] [Google Scholar]
  38. Wiśniewski H. M., Ghetti B., Terry R. D. Neuritic (senile) plaques and filamentous changes in aged rhesus monkeys. J Neuropathol Exp Neurol. 1973 Oct;32(4):566–584. doi: 10.1097/00005072-197310000-00007. [DOI] [PubMed] [Google Scholar]
  39. Wiśniewski H., Johnson A. B., Raine C. S., Kay W. J., Terry R. D. Senile plaques and cerebral amyloidosis in aged dogs. A histochemical and ultrastructural study. Lab Invest. 1970 Sep;23(3):287–296. [PubMed] [Google Scholar]
  40. Yamada T., Sasaki H., Dohura K., Goto I., Sakaki Y. Structure and expression of the alternatively-spliced forms of mRNA for the mouse homolog of Alzheimer's disease amyloid beta protein precursor. Biochem Biophys Res Commun. 1989 Feb 15;158(3):906–912. doi: 10.1016/0006-291x(89)92808-8. [DOI] [PubMed] [Google Scholar]
  41. Zimmermann K., Herget T., Salbaum J. M., Schubert W., Hilbich C., Cramer M., Masters C. L., Multhaup G., Kang J., Lemaire H. G. Localization of the putative precursor of Alzheimer's disease-specific amyloid at nuclear envelopes of adult human muscle. EMBO J. 1988 Feb;7(2):367–372. doi: 10.1002/j.1460-2075.1988.tb02822.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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